LB-4. Fidaxomicin Shows Early Superiority over Vancomycin on Intention-To-Treat Analyses of Pivotal Randomized Controlled Trials in Clostridium difficile Infection
Session: Poster Abstract Session: Late Breaker Posters
Saturday, October 22, 2011
Room: Poster Hall B1

Background: A recently completed phase 3 trial, study 003, showed fidaxomicin to be non-inferior to vancomycin for curing C. difficile infection (CDI) and superior for reducing CDI recurrence. A second study, 004, has recently completed.

Methods: In both studies, adults with active CDI were randomised to receive blinded fidaxomicin 200 mg twice daily or vancomycin 125 mg four times a day for 10 days. Study 004 was analysed by the same pre-specified analysis plan as study 003. Post-hoc exploratory intention-to-treat (ITT) time-to-event analyses were undertaken on the combined study 003 and 004 data, using fixed-effects meta-analysis and Cox regression models, and fixing the time of the 8-12 day primary end of therapy assessment at 12 days.

Results: A total of 535 patients were recruited into study 004. Results of pre-specified primary and secondary outcomes were highly similar to study 003, with fidaxomicin being non-inferior for clinical cure and superior for reducing CDI recurrence compared to vancomycin. ITT analysis of the combined data on 1164 patients showed fidaxomicin reduced persistent diarrhea, recurrence or death by 40% (95% CI 26-51%; p<0.0001) compared to vancomycin overall through day 40. A 37% (95% CI 2-60%, p=0.037) reduction in persistent diarrhea or death was evident through day 12 (heterogeneity p=0.50 vs 13-40 days), driven by 7 (1.2%) fidaxomicin vs 17 (2.9%) vancomycin deaths through 12 days (exact p=0.06) (Figure). Low albumin and eosinophil counts, and use of metronidazole/vancomycin before randomization, were risk factors for persistent diarrhea/death through 12 days and CDI in the previous 3 months was a risk factor for relapse (all p<0.01).

Conclusion: Fidaxomicin is a promising new agent for improving outcomes following C. difficile infection.


Subject Category: A. Antimicrobial agents and Resistance

A. Sarah Walker, PhD1, Derrick Crook, MB BCh1, Yin Kean2, Karl Weiss, MD3,4, Oliver Cornely, MD, FIDSA5, M Miller, MD6, Roberto Esposito7, Thomas Louie, M D8, Nicole Stoesser1, Bernadette Young, MBBS1, Brian Angus1, Sherwood Gorbach, MD, FIDSA2 and Tim Peto, MB BS, DPhil1, (1)NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom, (2)Optimer Pharmaceuticals, San Diego, CA, (3)Division of Infectious Diseases, Jewish Hospital, McGill University, Montreal, QC, Canada, (4)Hop. Maisonneuve-Rosemont, Montreal, QC, Canada, (5)University of Cologne, Koeln, Germany, (6)Jewish General Hospital, Montreal, QC, Canada, (7)Clinica delle Malattie Infetive e Tropicali, Modena, Italy, (8)University of Calgary, Calgary, AB, Canada

Disclosures:

A. S. Walker, None

D. Crook, Optimer Pharmaceuticals: Investigator and Scientific Advisor, Consulting fee and Institution received per-case funding to support trial patient expenses

Y. Kean, Optimer Pharmaceuticals: Employee, Salary

K. Weiss, Optimer Pharmaceuticals: Investigator, Institution received per-case funding

O. Cornely, Optimer: Investigator, Research support

M. Miller, Optimer Pharmaceuticals: Investigator and Scientific Advisor, Institution received per-case funding; travel to meetings and Speaker honorarium

R. Esposito, Optimer Pharmaceuticals: Investigator, Institution received per-case funding

T. Louie, Optimer Pharmaceuticals: Investigator, Listed on fidaxomixin patent and Scientific Advisor, Institution received per case funding; travel to meetings and Speaker honorarium

N. Stoesser, None

B. Young, None

B. Angus, None

S. Gorbach, Optimer: Board Member, Salary

T. Peto, Optimer Pharmaceuticals: Scientific Advisor, Consulting fee

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